Bacillus Calmette-Guérin Vaccination Status Research Articles

BCG vaccination and multiple sclerosis risk: A Norwegian cohort study

Introduction: Bacillus Calmette–Guérin (BCG) vaccination induces long-lasting effects on the adaptive and innate immune systems and prevents development of experimental autoimmune encephalomyelitis and possibly also inflammatory disease activity in multiple sclerosis (MS). Objective: The objective is to examine if BCG given in early adulthood decreases MS risk. Methods: From 791,369 (52% females) Norwegians participating in a national tuberculosis screening program from 1963 to 1975, we collected information on BCG vaccination and tuberculosis disease status. Later, MS disease was ascertained through both the Norwegian MS Registry and Biobank and the Norwegian Death Registry. We used logistic regression models to assess the relationship between BCG vaccination and MS risk. Results: In those BCG vaccinated, mean age at vaccination was 15.6 (standard deviation (SD) = 5.5) years. A total of 2862 (65% females) MS cases were retrieved. Overall, we found no association between MS risk and BCG vaccination. Compared to non-BCG-vaccinated individuals with no signs of tuberculosis infection, odds ratio (OR) for MS was 1.00 (95% confidence interval (CI) = 0.80–1.25) in the BCG-vaccinated group. In those not BCG vaccinated because of latent tuberculosis infection, the corresponding OR was 0.86 (95% CI = 0.66–1.13). Conclusion: We found no evidence of BCG vaccination or latent tuberculosis infection in young adulthood being linked to MS risk.

Mouse Subcutaneous BCG Vaccination and Mycobacterium tuberculosis Infection Alter the Lung and Gut Microbiota.

ABSTRACTThe objective of this study was to characterize the effect of Bacillus Calmette-Guérin (BCG) vaccination and M. tuberculosis infection on gut and lung microbiota of C57BL/6 mice, a well-characterized mouse model of tuberculosis. BCG vaccination and infection with M. tuberculosis altered the relative abundance of Firmicutes and Bacteroidetes phyla in the lung compared with control group. Vaccination and infection changed the alpha- and beta-diversity in both the gut and the lung. However, lung diversity was the most affected organ after BCG vaccination and M. tuberculosis infection. Focusing on the gut–lung axis, a multivariate regression approach was used to compare profile evolution of gut and lung microbiota. More genera have modified relative abundances associated with BCG vaccination status at gut level compared with lung. Conversely, genera with modified relative abundances associated with M. tuberculosis infection were numerous at lung level. These results indicated that the host local response against infection impacted the whole microbial flora, while the immune response after vaccination modified mainly the gut microbiota. This study showed that a subcutaneous vaccination with a live attenuated microorganism induced both gut and lung dysbiosis that may play a key role in the immunopathogenesis of tuberculosis.IMPORTANCE The microbial communities in gut and lung are important players that may modulate the immunity against tuberculosis or other infections as well as impact the vaccine efficacy. We discovered that vaccination through the subcutaneous route affect the composition of gut and lung bacteria, and this might influence susceptibility and defense mechanisms against tuberculosis. Through these studies, we can identify microbial communities that can be manipulated to improve vaccine response and develop treatment adjuvants.

Factors determining COVID-19 pneumonia severity in a country with routine BCG vaccination.

The impact of countries' bacillus Calmette-Guérin (BCG) vaccination policies on the course of coronavirus disease (COVID-19) outbreak is a curiosity. In this study, the relationship between BCG vaccination status and severity of COVID-19 pneumonia and the factors affecting disease severity were investigated. A retrospective cross-sectional study was conducted between March and June 2020 in patients diagnosed with COVID-19 pneumonia, confirmed by severe acute respiratory syndrome coronavirus-2 polymerase chain reaction positivity in a nasopharyngeal sample and pulmonary infiltrates in computed chest tomography, in a state hospital in Istanbul, Turkey. Socio-demographic features, body mass index, smoking status, concomitant diseases, income rates and BCG vaccination status of subjects were analyzed. The study population comprised 123 adults with COVID-19 pneumonia [mean age=49·7 years, standard deviation=13·3 years; 82 (66·7%) male]. While the rate of cases vaccinated with BCG is lower (68·5 versus 88·2%, P=0·026), mean age (54·0±11·5 years versus 38·3±10·7 years; P<0·001), diabetes (32·6 versus 5·9%, P=0·002) and low income (84·3 versus 52·9%, P<0·001) are higher in patients with severe disease compared to those with mild disease. According to multivariate analysis increasing age [odds ratio (OR)=1·119; 95% confidence interval (CI)= 1·062-1·178, P<0·001] and low income (OR=3·209; 95% CI=1·008-10·222, P=0·049) are associated with severe disease in COVID-19 pneumonia. This study reveals that BCG vaccination is not associated with disease severity in COVID-19 pneumonia. Age and low income are the main determinants of severe COVID-19 pneumonia.

BCG vaccination protects against infection with Mycobacterium tuberculosis ascertained by tuberculin skin testing

There is conflicting evidence as to whether Bacillus Calmette-Guérin (BCG) vaccination offers protection against Mycobacterium tuberculosis infection ascertained by a positive tuberculin skin test (TST). We investigated the association between BCG vaccination status and TST results in a set of surveys at increasing TST cut-off values to take cross-reactions to BCG vaccination into account. Secondary analysis of data from three consecutive tuberculin surveys done among schoolchildren in Tanzania between 1990 and 2002. BCG vaccination status was ascertained by the presence of a typical scar. We analyzed data of 277,588 children of whom 77.7% were BCG vaccinated and 8.5% had TST indurations ≥ 15 mm, 5.1% ≥ 17 mm and 2.8% ≥ 19 mm. In the combined analysis, odds ratios for a positive TST were > 1 for children with BCG up to TST cut-off values of 16 mm. For cut-off values > 17 mm crude and adjusted odds ratios were significantly < 1, and decreased with further increasing cut-off values. Using a methodology that makes use of the differences in TST reaction sizes between specific and non-specific responses, we showed that BCG vaccination was associated with reduced prevalence of M. tuberculosis infection as measured by the tuberculin skin test, suggesting a protective effect.

Observational study to estimate the changes in the effectiveness of bacillus Calmette-Guérin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK.

Until recently, evidence that protection from the bacillus Calmette-Guérin (BCG) vaccination lasted beyond 10 years was limited. In the past few years, studies in Brazil and the USA (in Native Americans) have suggested that protection from BCG vaccination against tuberculosis (TB) in childhood can last for several decades. The UK's universal school-age BCG vaccination programme was stopped in 2005 and the programme of selective vaccination of high-risk (usually ethnic minority) infants was enhanced. To assess the duration of protection of infant and school-age BCG vaccination against TB in the UK. Two case-control studies of the duration of protection of BCG vaccination were conducted, the first on minority ethnic groups who were eligible for infant BCG vaccination 0-19 years earlier and the second on white subjects eligible for school-age BCG vaccination 10-29 years earlier. TB cases were selected from notifications to the UK national Enhanced Tuberculosis Surveillance system from 2003 to 2012. Population-based control subjects, frequency matched for age, were recruited. BCG vaccination status was established from BCG records, scar reading and BCG history. Information on potential confounders was collected using computer-assisted interviews. Vaccine effectiveness was estimated as a function of time since vaccination, using a case-cohort analysis based on Cox regression. In the infant BCG study, vaccination status was determined using vaccination records as recall was poor and concordance between records and scar reading was limited. A protective effect was seen up to 10 years following infant vaccination [< 5 years since vaccination: vaccine effectiveness (VE) 66%, 95% confidence interval (CI) 17% to 86%; 5-10 years since vaccination: VE 75%, 95% CI 43% to 89%], but there was weak evidence of an effect 10-15 years after vaccination (VE 36%, 95% CI negative to 77%; p = 0.396). The analyses of the protective effect of infant BCG vaccination were adjusted for confounders, including birth cohort and ethnicity. For school-aged BCG vaccination, VE was 51% (95% CI 21% to 69%) 10-15 years after vaccination and 57% (95% CI 33% to 72%) 15-20 years after vaccination, beyond which time protection appeared to wane. Ascertainment of vaccination status was based on self-reported history and scar reading. The difficulty in examining vaccination sites in older women in the high-risk minority ethnic study population and the sparsity of vaccine record data in the later time periods precluded robust assessment of protection from infant BCG vaccination > 10 years after vaccination. Infant BCG vaccination in a population at high risk for TB was shown to provide protection for at least 10 years, whereas in the white population school-age vaccination was shown to provide protection for at least 20 years. This evidence may inform TB vaccination programmes (e.g. the timing of administration of improved TB vaccines, if they become available) and cost-effectiveness studies. Methods to deal with missing record data in the infant study could be explored, including the use of scar reading. The National Institute for Health Research Health Technology Assessment programme. During the conduct of the study, Jonathan Sterne, Ibrahim Abubakar and Laura C Rodrigues received other funding from NIHR; Ibrahim Abubakar and Laura C Rodrigues have also received funding from the Medical Research Council. Punam Mangtani received funding from the Biotechnology and Biological Sciences Research Council.

Tuberculin and QuantiFERON-TB-Gold tests for latent tuberculosis: a meta-analysis.

Up to now, there has been no universal consensus on the agreement between the tuberculin skin test (TST) and the QuantiFERON-TB-Gold test (QFT) in the detection of latent tuberculosis infection (LTBI) among high-risk populations. To estimate the agreement between TST and QFT among health care workers (HCWs). A meta-analysis in which all major electronic databases, including Medline, Scopus, Web of Sciences and Ovid, were searched until June 2014. All cross-sectional and cohort studies addressing the agreement between TST and the QFT were included. The extracted data were analysed and the results were reported using random effect models. The overall kappa statistic between TST and the QFT was 0.27 [95% confidence interval (CI) 0.22, 0.32] and the adjusted kappa statistic for prevalence and bias was 0.41 (95% CI 0.32, 0.50). The kappa for subjects with and without bacillus Calmette-Guérin (BCG) vaccination was 0.27 (95% CI 0.18, 0.36) and 0.31 (95% CI 0.15, 0.46) respectively. The figures were 0.30 (95% CI 0.16, 0.43) and 0.82 (95% CI 0.74, 0.90) for prevalence-adjusted and bias-adjusted kappa, respectively. The overall agreement between TST and QFT in the detection of LTBI among HCWs was poor. After adjusting for the prevalence and bias indices, kappa statistics reached fair agreement. The utility of each of these two tests is dependent on the prevalence and burden of tuberculosis as well as the BCG vaccination status.

Individual-level factors associated with variation in mycobacterial-specific immune response: Gender and previous BCG vaccination status

A more effective tuberculosis (TB) vaccine is needed to eliminate TB disease. Many new vaccine candidates enhance the immunogenicity of the existing vaccine, Bacillus Calmette-Guérin (BCG). Understanding BCG induced immune variation is key to developing a new vaccine. We aimed to establish if individual-level covariates were associated with cell-mediated immune response (interferon gamma (IFN-γ)) at vaccine trial enrolment (baseline) in a long-term retrospective analysis (LTR) and after BCG vaccination in a short-term prospective analysis (STP). Four covariates were analysed: gender, country, BCG vaccination history and monocyte/lymphocyte cell count ratio. Univariable and multivariable linear regression were conducted on IFN-γ response at baseline for LTR, and area under the curve (AUC), 24 week and peak IFN-γ response for STP. Previous BCG vaccination was strongly associated with higher IFN-γ response at baseline (LTR analysis) (p-values < 0.05). Being male showed a weak association with higher baseline response (p-value = 0.1). BCG revaccination was strongly associated with a larger response increase than primary-vaccination (AUC & peak p-values < 0.01), but did not differ at 24 weeks (STP analysis). All other covariates were non-significant (p-values > 0.1). This analysis suggests that previous BCG vaccination and gender are associated with durable IFN-γ responses. Vaccine trials may need to stratify by BCG vaccination history and gender.

Bacillus Calmette–Guérin is a preventive factor in mortality of childhood tuberculous meningitis

Studies have been done that have focused on the efficacy of bacillus Calmette-Guérin (BCG) vaccination in the prevention of cases of childhood tuberculous meningitis (TBM). However the efficacy of the vaccination in the prevention of mortality has not been sufficiently evaluated. This study aimed to determine the main features of TBM cases in childhood and to evaluate the factors related to mortality, proving the protective effect of BCG vaccination in childhood TBM. In a retrospective approach, all consecutive cases of TBM in children that occurred between 1997 and 2005, at Dicle University Hospital, were studied. The following data were evaluated: demographic aspects, admission symptoms, radiology and laboratory findings, BCG vaccination status, tuberculin skin test (TST) positivity, and mortality rates. In total, 172 cases of childhood TBM were evaluated (mean age 53.3±55.7 months; 109 boys (63.4%)). The majority of these cases (70.4%) had typical TBM symptoms on admission. BCG vaccination data were available for 152 (88.4%) cases and 29 of them (19.1%) were positive. The TST was performed for 143 patients (83.1%) and 28 (19.6%) were found positive. Hydrocephalus was identified in 118 patients (68.6%) on computed tomography examination. A shunt was placed in 79 cases (45.9%). In total, 24 patients (14.0%) died in the hospital. TST negativity was a significant factor for mortality (p=0.012). BCG positivity was found to be a preventive factor from mortality (p=0.05). BCG vaccination is effective in the prevention of TBM-associated mortality in childhood. TST negativity may be a sign of a poor prognosis in TBM cases.

Specific detection of tuberculosis infection: an interferon-gamma-based assay using new antigens.

The tuberculin skin test for immunologic diagnosis of Mycobacterium tuberculosis infection has many limitations, including being confounded by bacillus Calmette-Guérin (BCG) vaccination or exposure to nontuberculous mycobacteria. M. tuberculosis-specific antigens that are absent from BCG and most nontuberculous mycobacteria have been identified. We examined the use of two of these antigens, CFP-10 and ESAT-6, in a whole blood IFN-gamma assay as a diagnostic test for tuberculosis in BCG-vaccinated individuals. Because of the lack of an accurate standard with which to compare new tests for M. tuberculosis infection, specificity of the whole blood IFN-gamma assay was estimated on the basis of data from people with no identified risk for M. tuberculosis exposure (216 BCG-vaccinated Japanese adults) and sensitivity was estimated on the basis of data from 118 patients with culture-confirmed M. tuberculosis infection who had received less than 1 week of treatment. Using a combination of CFP-10 and ESAT-6 responses, the specificity of the test for the low-risk group was 98.1% and the sensitivity for patients with M. tuberculosis infection was 89.0%. The results demonstrate that the whole blood IFN-gamma assay using CFP-10 and ESAT-6 was highly specific and sensitive for M. tuberculosis infection and was unaffected by BCG vaccination status.

Determination of the Prevalence of Infection with Mycobacterium tuberculosis among Persons Vaccinated against Bacillus Calmette-Guerin in South Korea

The prevalence of tuberculous infection was estimated among 12,032 persons with a Bacillus Calmette-Guérin (BCG) vaccination scar and 7,788 persons without such a scar who participated in a nationwide tuberculin skin test survey conducted in the Republic of Korea in 1975. The analysis was built upon mixture models that captured the heterogeneity of indurations arising from tuberculous infection, cross-reactions due to infection with environmental mycobacteria, and BCG vaccination. The three distributions were allowed to vary by age, sex, and BCG vaccination status in the Bayesian manner, according to the prior opinion of the authors. Estimated prevalences of tuberculous infection were similar among persons with a BCG scar and persons without one: 7.5% (95% credibility interval (CI): 3.1, 12.5) and 5.2% (95% CI: 4.2, 6.3), respectively, at age 0-4 years and 87.3% (95% CI: 84.0, 90.2) and 84.0% (95% CI: 81.9, 85.8), respectively, at age 25-29 years. From this analysis it can be concluded that mixture models allow investigators, for the first time, to estimate the prevalence of tuberculous infection not only in unvaccinated persons but also in the BCG-vaccinated population. Mixture models are a versatile tool for analyzing diagnostic test data and more general classification problems of considerable complexity.

Epidemiology of Buruli ulcer in Amansie West district, Ghana

This paper describes 90 cases of Buruli ulcer in Amansie West district, Ghana. 49% were below 15 years of age while 20% were over 50 years. There was a significant difference in the age and sex composition, with more males among the younger age groups than females but the converse among adults. Seasonal variation is described, with peak incidence in September and October. Cases who had received bacillus Calmette-Guérin (BCG) vaccination had a shorter duration of the ulcer than those who were not vaccinated. No such association was found between BCG vaccination and the age of onset of the disease. There was no significant difference between cases and controls regarding their BCG vaccination status. There is an urgent need to regard Buruli ulcer in Ghana more seriously.